Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage.

TitleMultivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage.
Publication TypeJournal Article
Year of Publication2023
AuthorsAguilar R, Khan L, Arslanovic N, Birmingham K, Kasliwal K, Posnikoff S, Chakraborty U, Hickman AR, Watson R, Ezell RJ, Willis HE, Cowles MW, Garner R, Shim A, Gutierrez I, Marunde MR, Keogh M-C, Tyler JK
JournalRes Sq
Date Published2023 Jul 28
Abstract

Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends the lifespan of budding yeast exposed to chronic oxidative genotoxicity. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.

DOI10.21203/rs.3.rs-3182883/v1
Alternate JournalRes Sq
PubMed ID37546815
PubMed Central IDPMC10402244
Grant ListR44 GM136172 / GM / NIGMS NIH HHS / United States
R44 GM117683 / GM / NIGMS NIH HHS / United States
R44 HG010640 / HG / NHGRI NIH HHS / United States
R44 CA212733 / CA / NCI NIH HHS / United States
R01 CA095641 / CA / NCI NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States
R35 GM139816 / GM / NIGMS NIH HHS / United States
R01 AG079883 / AG / NIA NIH HHS / United States
Related Faculty: 
Jessica K. Tyler, Ph.D.

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